Angiotensin converting enzyme (ACE) is present mainly in human vascular endothelial cells, lungs, kidneys and the brain. This enzyme may remove two amino acid residues (His-Leu) from the C-terminus of the inactivated angiotensin I to form an activated angiotensin II so as to cause contraction of blood vessels and increase blood pressure (Maruyama, S. and Suzuki, H., A peptide inhibitor of angiotensin I converting enzyme in the tryptic hydrolysate of casein, Agric. Biol. Chem., 1982, 46: 1393-1394). Maruyama, S. et al. (Angiotensin I-converting enzyme inhibitor derived from an enzymatic hydrolysate of casein. II. Isolation and bradykinin-potentiating activity on the uterus and the ileum of rats, Agric. Biol. Chem., 1985; 49: 1405-1409) found that ACE may inactivate bradykinin (having blood vessel dilating activity) so as to increase blood pressure. Therefore, the binding of an angiotensin converting enzyme inhibitor (ACEI) with ACE may reduce the formation of angiotensin II and the inactivation of bradykinin, so application of an ACEI may ameliorate hypertensive symptoms.
Krysiak, R. et al, (The effect of angiotensin-converting enzyme inhibitors on plasma adipokine levels in normotensive patients with coronary artery disease, Polish Journal of Endocrinology, 2010, 61: 280-286) discloses that ACE inhibitors are effective agents in patients with coronary artery disease (CAD), even if their blood pressure is within normal limits. U.S. Pat. No. 8,021,697 B2 discloses that ACE inhibitors can alter the distribution of body mass by decreasing overall percentage of fat and/or increasing the ratio of lean mass to fat mass. In other words, ACE inhibitors can reduce the amount of fat that is produced from consumed food.
In addition to chemically synthesized drugs, it has been found that many peptides having different lengths and amino acid residues can effectively inhibit ACE. The peptides having ACE inhibitory activity can be isolated from foods including, e.g., hydrolysates of animal or plant proteins, such as casein (Maruyama and Suzuki, 1982; Maruyama, S. and Suzuki, H., 1985; and Yamamoto, N. et al., Antihypertensive effect of peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790, J. Dairy Sci., 1994, 77: 917-922), corn protein (e.g., α-zein) (Miyoshi et al., Structures and activity of angiotensin-converting enzyme inhibitors in an α-zein hydrolysate, Agric. Biol. Chem., 1991, 55: 1313-1318 and Yano, S. et al., Isolation from α-zein of thermolysin peptides with angiotensin I-converting enzyme inhibitory activity, Biosci. Biotech. Biochem., 1996, 60: 661-663), sardine (Matsui, T. et al., Inhibition of angiotensin I-converting enzyme by Bacillus licheniformis alkaline protease hydrolyzates derived from sardine muscle, Biosci. Biotech. Biochem., 1993, 57: 922-925 and Matsufuji, H. Et al., Angiotensin I-converting enzyme inhibitory peptides in an alkaline protease hydrolyzate derived from sardine muscle, Biosci. Biotech. Biochem., 1994, 58: 2244-2245) and bonito (Matsumura, N. et al., Isolation and characterization of angiotensin I-converting enzyme inhibitory peptides derived from bonito bowels, Biosci. Biotech. Biochem., 1993, 57: 1743-1744 and Fujita, H. et al., Antihypertensive effect of thermolysin digest of dried bonito in spontaneously hypertensive rat, Clin. Exp. Pharmacol. Physiol. Suppl., 1995, 22: S304-S305), and fermented foods, such as sake and wine residue (Saito, Y. et al., Structure and activity of angiotensin I converting enzyme inhibitory peptides from sake and sake lees, Biosci. Biotechnol. Biochem., 1994, 58: 1767-1771), soy sauce (Kinoshita, E. et al., Purification and identification of an angiotensin I-converting enzyme inhibitor from soy sauce, Biosci. Biotechnol. Biochem., 1993, 57: 1107-1110), cheese (Okamoto, A. et al., Angiotensin I converting enzyme inhibitory activities of various fermented foods, Biosci. Biotechnol. Biochem., 1995, 59: 1147-1149) and sour milk (Masuda, O. et al., Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats, J. Nutr., 1996, 126: 3063-3068).
JP7289281 (A) discloses that the fermented product of soy bean with Aspergillus niger has ACE inhibitory activity. JP4299991 (A) discloses that a peptide product obtained by hydrolyzing soy bean with bromelain (a proteinase) has ACE inhibitory activity. JP2002053595 (A) discloses that the peptides from a soy bean hydrolysate can inhibit ACE activity. JP6298794 (A) discloses a process for the preparation of ACEI from the proteins of animal and plant sources, such as fish meats, pork and chicken. The hydrolysate is subjected to centrifugation, filtration, concentration and resin absorption to obtain the peptides with ACE inhibitory activity. JP5331192 (A) discloses that dried katsuobushi can be hydrolyzed by thermolysin to produce a peptide with ACE inhibitory activity. JP4264098 (A) discloses the preparation of a peptide with ACE inhibitory activity from chicken meat containing no fat. U.S. Pat. No. 5,854,029 discloses a process for the preparation of a dipeptide exhibiting ACE inhibitory activity. U.S. Pat. No. 6,767,990 B1 discloses peptides isolated from the hydrolysate of chicken residue. US 20120107409 A1 discloses a method for preparing a fish skin fermentation product which can inhibit the activity of tyrosinase, inhibit the activity of angiotensin-converting enzyme and/or improve the survival of fibroblasts.
A need still exists in the art for ACE inhibitors, particularly peptides from natural sources, which are more safe than the chemically synthesized compounds.